Endometrial cancer incidence is rising, with 435,000 global cases in 2019. An effective, low cost primary prevention strategy is required to reduce disease burden. Obesity, insulin resistance and inflammation contribute to endometrial carcinogenesis and physical activity targets these pathways. This study sought to quantify the amount of physical activity required to impact upon endometrial cancer risk. Physical activity data from 222,031 female participants with an intact uterus in the UK Biobank study were analysed using a multi-variable Cox proportional hazards model. A systematic review of the literature was performed, searching CENTRAL, Embase and MEDLINE databases up to 19/04/2021. Studies including participants with and without endometrial cancer investigating the effect of physical activity measured in MET-h/week on disease risk were included. Two reviewers independently selected studies, extracted data and evaluated the risk of bias. Within the UK Biobank, each 1 MET-h/week increase in total physical activity was associated with a 0.2% (95%CI 0.1-0.4%, p=0.020) reduction in endometrial cancer risk, equating to a 10.4% reduction if performing 50 MET-h/week or 7 hours of jogging/week. Eleven cohort and 12 case-control studies were identified in the systematic review, including 821,599 participants. One study reported a non-significant effect of 1 MET-h/week increases in physical activity on endometrial cancer risk (OR 1.00, 95%CI 0.99-1.00). Eight studies found significant reductions in disease risk of 15-53%, but only in the most physically active individuals. Physical activity reduces endometrial cancer risk, but the effect size appears small. Regular vigorous activity should be encouraged to maximise the health benefit observed.

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